Genitourinary Syndrome of Menopause

Genitourinary Syndrome of Menopause 

6 Interesting Facts of Genitourinary Syndrome of Menopause 

1. Genitourinary syndrome of menopause is a collection of signs and symptoms associated with postmenopausal-reduced estrogen and other sex steroids that lead to changes in the labia, clitoris, vestibule/introitus, vagina, urethra, and bladder
2. Primary symptoms include, but are not limited to:
   • Urinary: urgency, dysuria, frequency, and recurrent urinary tract infections
   • Genital: dryness, burning, and irritation
   • Sexual: lack of lubrication, impaired function, and dyspareunia
3. In most women, diagnosis is established by clinical presentation; both history and examination are needed
4. Treatment options include nonhormonal methods (moisturizers, lubricants, vaginal dilation) and hormones
   • Mild to moderate symptoms: preferred initial treatment is nonprescription vaginal lubricants and moisturizers
   • Moderate to severe symptoms and symptoms unresponsive to nonprescription therapy: first line treatment is low-dose vaginal estrogen when patient has no contraindications. Vaginal estrogen preparations may be used alone or in combination with vaginal lubricants and moisturizers
   • Alternative approved treatment options include selective estrogen receptor modulators and vaginal dehydroepiandrosterone
5. Ask women nearing menopause if they are experiencing any symptoms; most will not initiate discussion about symptoms with health care providers
6. Prognosis is excellent for women with symptoms that are responsive to standard care; symptoms are unlikely to resolve without treatment

Pitfalls

• Many women do not initiate discussion with health care providers despite significant symptoms (eg, urinary tract infection, genital irritation, sexual dysfunction); therefore, syndrome is underdiagnosed and undertreated
  • Maintain awareness to ask about symptoms; effective treatment is available. Untreated symptoms can lead to worsening sexual dysfunction and vaginal stenosis
• Genitourinary syndrome of menopause poses some diagnostic challenges 
  • Many women with mild to moderate signs of syndrome on examination remain asymptomatic
  • Symptoms often correlate poorly with physical examination findings
• Infectious or inflammatory vaginitis may coexist with syndrome
  • Concern for presence of concomitant diagnosis requires separate evaluation and treatment when indicated
• Weigh risks and benefits of treatment options (eg, vaginal hormonal treatments) in women with history of hormone-sensitive cancers (eg, breast cancer) 

• Genitourinary syndrome of menopause is a collection of signs and symptoms associated with postmenopausal reduced estrogen and other sex steroids that lead to changes in the labia, clitoris, vestibule/introitus, vagina, urethra, and bladder
• Primary symptoms include but are not limited to: 
  • Urinary: urgency, dysuria, frequency, and recurrent urinary tract infections
  • Genital: dryness, burning, and irritation
  • Sexual: lack of lubrication, impaired function, and dyspareunia
• Terms previously used to describe this condition include vulvovaginal atrophy, vaginal atrophy, and atrophic vaginitis 

Classification

• By cause 
  • Hypoestrogenism due to natural menopause
  • Hypoestrogenic states occurring for reasons other than natural menopause
    • Surgical menopause (bilateral oophorectomy with or without hysterectomy)
    • Primary ovarian insufficiency
    • Hypothalamic amenorrhea
    • Postpartum state and breastfeeding
    • Medications (eg, gonadotropin-releasing hormone agonists, aromatase inhibitors)
    • Cancer treatments such as surgery, pelvic radiation therapy, or chemotherapy that render ovaries inactive

Diagnosis

Clinical Presentation

History

• Many women do not self-report symptoms and must be asked about them specifically
  • Minority of postmenopausal women initiate conversation about vaginal symptoms with their health care provider; about 25% of women with genitourinary syndrome of menopause actually seek treatment
    • Women may consider symptoms to be part of aging and be unaware of possible treatments
  • Up to 50% of women with signs lack symptoms 
  • Symptom severity may be reported as minor, bothersome, or significant, affecting sexual health and/or quality of life
  • Most common symptoms are vaginal dryness (up to 75%) and dyspareunia (up to 44%)
  • Severe symptoms may cause discomfort with sitting and bathroom hygiene (wiping) and provoke avoidance of sexual activity 
  • Symptoms may develop or persist despite receiving systemic estrogen replacement therapy prescribed for other menopausal symptoms
• Urologic symptoms
  • Frequency, urgency, dysuria, and hematuria
  • Postvoid dribbling
  • Nocturia
  • Stress and/or urge incontinence
  • Recurrent urinary tract infections
• Genital symptoms
  • Vulvar irritation, itching, and burning
  • Vulvodynia (pain involving vulva); vaginal, pelvic, and suprapubic pain or pressure
  • Vaginal dryness, irritation, pruritus, and burning
  • Vaginal discharge, which varies (eg, watery, yellow, brownish, blood-tinged, bloody)
• Sexual symptoms
  • Loss of libido and arousal
  • Lack of lubrication
  • Dyspareunia
  • Dysorgasmia
  • Pelvic pain
  • Coital or postcoital bleeding or spotting

Physical examination

• General issues regarding examination
  • More than half of women will show signs of the condition on vaginal examination 4 years postmenopause 
  • Assess for presence and degree of vaginal introital stenosis with digital examination before inserting speculum to avoid trauma; may need smaller (eg, pediatric) speculum
    • May need to defer direct vaginal examination for patients with severe stenosis of vaginal introitus; instead, may need to use vaginoscopy to allow visualization
  • Use adequate lubricant during examination, which may be performed with topical anesthesia, if necessary
• External genitalia findings 
  • Thinning or graying pubic hair
  • Thinning and resorption of the labia minora; labia minora may fuse
  • Loss of labial fat pad
    • Renders appearance of labia majora as more pendulous and clitoris more prominent
  • Decreased width of introitus; introital stenosis (defined as width of fewer than 2 fingers) may develop
  • Loss of hymenal remnants
  • Prominent urethral meatus and/or urethral caruncula (erythematous polypoid tissue proliferation involving urethral meatus)
• Internal examination findings 
  • Diminished vaginal caliber and depth
  • Shiny and pale vaginal mucosa
  • Decreased vaginal rugae and elasticity
  • Cervical flush (cervix becomes flush with vaginal vault and identifiable only as small opening in apex of vagina) and obliteration of vaginal fornices
  • Decreased vaginal secretions is typical; vaginal discharge may be present with concomitant inflammation
  • Signs of inflammation with vaginal erythema, friability, and easy bleeding
  • Signs of trauma (secondary to intercourse with lack of lubrication and thinning of mucosa) with mucosal petechiae, ecchymoses, abrasions, and lacerations

Causes

• Decline in estrogen is responsible for most symptoms; decrease in other sex steroids also may contribute (eg, low androgen levels)
  • Physiologic effects of hypoestrogenemia 
    • Loss of dermal collagen in vagina, bladder, and urethra; overall decrease in compliance of urogenital tissue
    • Decreased vaginal rugae and diminished vaginal elasticity
    • Decreased vaginal blood flow (estrogen is a vasoactive hormone)
    • Thinning and pallor of vaginal wall, bladder, and urethral epithelium
    • Vaginal pH increased to 5 or higher
    • Decreased lactobacilli and diminished diversity of species in bacterial microbiome
      • Lactobacilli may help prevent urogenital conditions (eg, bacterial vaginosis, yeast infection, urinary tract infection) 
      • Higher proportion of vaginal lactobacilli in postmenopausal women correlates inversely with vaginal dryness 
    • Decreased vaginal lubrication, related to decreased blood flow, decreased rugae, and change in the microbiome
    • Decreased sensory threshold when bladder is distended and impaired urethral closure pressure or urethral sphincter dysfunction, leading to urinary urgency, frequency, and incontinence
• Underlying causes:
  • Menopausal hypoestrogenism 
    • Natural menopause
  • Other causes of hypoestrogenism 
    • Surgical menopause (bilateral oophorectomy)
    • Ovarian failure
      • Premature ovarian failure
      • Pelvic radiation
      • Autoimmune disease affecting ovaries
    • Hypothalamic causes
      • Inadequate energy intake (eg, eating disorders, starvation)
      • Excessive energy expenditure (eg, extreme exercise)
    • Pituitary causes
      • Tumor or autoimmune pituitary destruction
    • Postpartum state 
      • Transient; duration depends on length of breastfeeding and may last 3 to 12 months
    • Hyperprolactinemia
      • Secondary to lactation or pituitary tumor
    • Pharmacotherapy
      • Gonadotropin-releasing hormone agonist (eg, leuprolide, nafarelin) and some gonadotropin-releasing hormone antagonists (eg, ganirelix, cetrorelix)
      • Specific selective estrogen receptor modulators (eg, tamoxifen)
      • Aromatase inhibitors
      • Danazol
      • Depot medroxyprogesterone acetate
      • Chemotherapeutic agents

Risk factors and/or associations

Age

• Condition is most commonly associated with natural menopause 
  • Average age for menopause in Western countries is 51 to 52 years 
  • Affects more than 50% of postmenopausal women 
• Less commonly may occur in premenopausal women
  • May be noted in prepubertal girls secondary to poorly estrogenized vaginal and vulvar tissue
  • May be noted in up to 15% of premenopausal women 

Ethnicity/race

• Black and Hispanic women in the United States reach menopause approximately 2 years earlier than White women 

Other risk factors/associations 

• Cigarette smoking
• Alcohol use disorder
• Decreased frequency of intercourse and sexual abstinence
• Lack of physical activity
• Absence of vaginal childbirth

Diagnostic Procedures

Primary diagnostic tools

• In most patients, diagnosis is established by clinical presentation 
  • Symptoms do not necessarily correlate with physical findings; therefore, both history and examination are needed to establish diagnosis 
• Ancillary studies are unnecessary for establishing diagnosis in most patients 
  • Testing may be performed in some patients to exclude alternate diagnosis and in patients with atypical presentation to strengthen suspicion of diagnosis
  • Cell cytology analysis (eg, Papanicolaou test, vaginal cytology, endometrial cytology) is required to exclude suspected malignancy
  • Imaging (eg, transvaginal ultrasonography) is indicated to evaluate patients with postmenopausal vaginal bleeding

Laboratory

• Vaginal ancillary tests that may strengthen suspicion for diagnosis:
  • Saline wet mount
    • Findings consistent with diagnosis include: 
      • More than 1 WBC per epithelial cell
      • Presence of parabasal cells (immature vaginal epithelial cells with relatively large nuclei)
      • Reduced or absent lactobacilli
  • Vaginal pH
    • Measure by placing litmus paper against lateral vaginal wall until moist 
    • Healthy estrogenized vagina (without infection or vaginitis) of an adult ranges from pH of 3.8 to 4.5 
    • pH of 5 or above is consistent with low estrogen state 
    • In the absence of bacterial pathogens, a vaginal pH of 6.0 to 7.5 strongly suggests a hypoestrogenemic state 
    • Certain infections (eg, bacterial vaginosis, trichomoniasis) may result in elevated vaginal pH
      • Elevated pH is common in premenopausal patients with pathologic bacterial pathogens 
    • Vaginal pH may be increased by presence of semen in the vagina, which also may confound pH testing results
  • Vaginal maturation index
    • Rarely used outside of research settings; performed on Papanicolaou test specimen
    • Quantifies estrogen status of vaginal epithelium as indicated by proportion of 3 types of epithelial cells collected from upper portion of vagina: 
      • Parabasal: least mature
      • Intermediate: moderately mature
      • Superficial: most mature
    • Predominance of parabasal cells and low proportion or absence of superficial epithelial cells is indicative of low circulating estrogen levels 
      • Less than 5% superficial cells is typical proportion in postmenopausal atrophic state 
    • Predominance of superficial and intermediate epithelial cells and absence of parabasal cells is indicative of higher circulating estrogen levels 
      • More than 15% superficial cells is considered within reference range for premenopausal state 
• Urinalysis
  • Useful to exclude alternative diagnosis when urinary symptoms predominate and to evaluate for urinary tract infection
  • Microscopic hematuria may be noted in patients with genitourinary syndrome of menopause
  • Pyuria and test results positive for leukocyte esterase and/or nitrates may indicate urinary tract infection; confirm with culture
• Vaginal swabs for nucleic acid amplification testing
  • Useful to exclude alternate diagnosis when symptoms of vaginal itching, burning, or discharge predominate
  • Vaginal swab can test for bacterial vaginosis, vaginal yeast infection, trichomoniasis, gonorrhea, and chlamydia. Commercial laboratories have swabs that are capable of testing for all in 1 test; alternatively, clinician may specify testing for individual pathogens based on clinical concern

Imaging

• Transvaginal ultrasonography
  • Useful for evaluating postmenopausal bleeding
    • Endometrium shows up as a dark line—sometimes called the endometrial stripe—and is examined to determine thickness of endometrial tissue
    • Average postmenopausal endometrial stripe is 5 mm or thinner (consistent with decreased estrogen stimulation) 
    • Thickened endometrial stripe raises suspicion for endometrial hyperplasia or endometrial cancer; endometrial biopsy is indicated
    • May need to perform hysteroscopy or dilation and curettage to further evaluate abnormal findings on transvaginal ultrasonography or endometrial biopsy
  • Useful for surveillance of women at high risk of endometrial cancer who are receiving long-term topical estrogen therapy or systemic estrogen therapy without opposing progestin

Differential Diagnosis

Most common

• Bacterial vaginosis
  • Common cause of vaginal discharge
  • Women with genitourinary syndrome of menopause are at increased risk for bacterial vaginosis
  • Presents similarly with various symptoms, including vaginal discharge associated with elevated pH, vaginal pruritus, and vaginal burning
  • Diagnose bacterial vaginosis with wet mount revealing clue cells and positive whiff test result (add potassium hydroxide to sample of discharge; if there is fishy odor, then whiff test result is positive)
  • Postmenopausal women often harbor more bacterial vaginosis–like organisms, and nucleic acid amplification may give a false-positive result for bacterial vaginosis
  • Resolution of symptoms after usual treatment of bacterial vaginosis may help to further differentiate diagnoses
  • Recurrence is not uncommon if concomitant genitourinary syndrome of menopause is not treated
• Candida vaginitis
  • Common cause of vaginal discharge
  • Women with genitourinary syndrome of menopause are at increased risk for Candida vaginitis
  • May present similarly with several symptoms, including vulvodynia, vulvar and vaginal pruritus, dysuria, and dyspareunia
  • Thick, clumpy, white discharge, intensely erythematous mucosa, discharge that is adherent to vaginal mucosa, and healthy vaginal pH is classic for Candida and may help to differentiate from genitourinary syndrome of menopause
  • Diagnose Candida vaginitis using potassium hydroxide preparation of discharge; may need to use culture or various molecular diagnostic methods (nucleic acid amplification) to confirm when diagnosis remains in question
  • Response to usual treatment of Candida vaginitis with topical or systemic antifungals may help to further differentiate diagnoses
• Vaginal trichomoniasis
  • Common cause of vaginitis; infection may be asymptomatic
  • Women with genitourinary syndrome of menopause are at increased risk for vaginal trichomoniasis
  • May present similarly with vaginal discharge, elevated vaginal pH, vulvar irritation, vulvar and vaginal pruritus, dysuria, postcoital bleeding or spotting, and dyspareunia
  • Purulent, green-yellow, frothy, malodorous discharge is more typical of symptomatic trichomoniasis than genitourinary syndrome of menopause; intensely inflamed cervix (colpitis macularis, also called strawberry cervix) is uncommon but highly suggestive of trichomoniasis
  • Confirm using wet mount, rapid antigen testing, or nucleic acid amplification testing
  • Response to usual treatment of trichomoniasis with metronidazole or tinidazole may help to further differentiate diagnoses
• Vulvar contact dermatitis
  • Common cause of perineal irritation. May be caused by contact with various products (eg, lubricants, moisturizers, powders, soaps, detergents, irritants in sanitary or bladder leakage pads, spermicides, condoms)
  • Women with genitourinary syndrome of menopause are at increased risk for perineal contact dermatitis and may be particularly vulnerable to contact dermatitis from lubricants or moisturizers
  • May present similarly with vulvar pruritus and burning, vulvodynia, dyspareunia, and perineal dryness. Findings range from erythema and scaling to fissuring with thickened, lichenified tissue primarily involving the labia majora
  • Diagnosis is established by clinical presentation with history of product use and examination findings in most patients
  • Response to usual treatment of contact dermatitis with discontinuation of offending agent and mild topical steroid, when necessary, may help to further differentiate diagnoses
• Lichen sclerosis 
  • Common problem affecting 1 in 300 to 1 in 1000 postmenopausal women; cause is uncertain
  • Associated with vulvar epithelial inflammation and thinning that does not extend to the vagina
  • Presents similarly with vulvar pruritus, burning, dryness, and vulvodynia
  • Dyspareunia may occur; rectal symptoms may develop (eg, pruritus ani, rectal bleeding)
  • May coexist with genitourinary syndrome of menopause
  • Classic appearance is hypopigmented, atrophic-appearing papules that may coalesce into plaques resulting in thin, wrinkled, parchment-looking skin in a figure-of-eight (keyhole) distribution around vulva and anus 
    • Purpura, fissures, and eventually lichenification may develop as a result of excoriation from scratching
    • Distinction between labia majora and minora may be lost
  • Lichen sclerosis is an important diagnostic consideration; a minority of older women with this diagnosis will have evidence of malignant epithelial changes or squamous cell neoplasia 
  • Diagnosis is based on clinical presentation; response to usual treatment of lichen sclerosis with potent topical steroid may help to further differentiate diagnoses. Treatment with topical estrogen is ineffective
  • Confirm diagnosis with vulvar biopsy showing characteristic histologic changes when diagnosis remains in question
• Lichen planus 
  • Idiopathic mucocutaneous inflammatory disease involving skin, hair, nails, and mucous membranes; skin and oral mucosa are the most commonly involved sites
  • Most commonly affects middle-aged adults; cause is unclear 
  • May coexist with genitourinary syndrome of menopause
  • Typical skin lesions are described as polygonal, hyperpigmented, erythematous, violaceous, flat-topped, pruritic papules with overlying reticular white striae without extension into vagina; severe disease may result in vaginal stenosis at the vaginal introitus
  • Oral lesions vary in appearance (eg, reticular, papular, plaque, atrophic, erosive) and often involve buccal mucosa, tongue, and gingiva
  • Vulvar lesions present similarly to genitourinary syndrome of menopause with irritation, pruritus, burning, pain, dryness, dysuria, and dyspareunia
  • Lesions may be difficult to differentiate from other dermatoses when vulva is involved; differentiate by clinical presentation and involvement of other areas of skin and mucous membranes
  • Response to usual treatment of lichen planus with topical steroids may help to further differentiate diagnoses; treatment with topical estrogen is ineffective
  • Confirm diagnosis with vulvar biopsy showing characteristic histologic changes when diagnosis remains in question
• Lichen simplex chronicus
  • Inflammatory condition involving the vulva that results secondary to vulvar pruritus and itching; underlying cause is often multifactorial and often includes elements of chronic irritation and allergic contact dermatitis
  • Presents similarly with vulvar pruritus, irritation, dryness, and dysuria secondary to excoriation
  • Characteristically, itching is somewhat relieved by rubbing or scratching, thus perpetuating a vicious itch-scratch cycle; examination findings usually reveal thickened, lichenified plaques with excoriations and accentuated skin markings 
  • Diagnosis is usually established by clinical presentation and response to usual treatment with topical corticosteroids
• Vulvar intraepithelial neoplasia
  • Worldwide, there are an estimated 5 cases per 100,000 women 
    • Becoming more common in young women
    • Oncogenic HPV is implicated in most cases
    • Cigarette smoking and HIV infection increase risk
  • Presents similarly either asymptomatically or with itching or burning of vulva
  • May coexist with genitourinary syndrome of menopause
  • Appearance on physical examination varies but is distinct from genitourinary syndrome of menopause, ranging from erythematous well-demarcated plaques to verrucalike white plaques, erosions, or hyperpigmented patches 
  • Confirm diagnosis with punch biopsy or excisional tissue biopsy revealing characteristic histology
• Vulvar cancer
  • Rare, affects 1 or 2 women in 10,000 annually 
    • Usually squamous cell, rarely adenocarcinoma or melanoma
    • Oncogenic HPV is implicated in most cases
  • Symptoms include itching, pain, and burning of the vulva not relieved by antifungals or steroid creams
  • Examination findings usually differentiate conditions; progressive thickening of skin with white or erythematous patches—and sometimes scaling—is characteristic of malignancy 
  • Over time, mass develops with ulceration, bleeding, and associated lymphadenopathy
  • Confirm diagnosis with punch biopsy or excisional tissue biopsy revealing characteristic histology 
• Vulvar Paget disease 
  • Usually presents clinically with eczemalike inflammatory skin changes overlying carcinoma of the breast; extramammary disease can manifest as vulvar intraepithelial adenocarcinoma
  • Condition is rare, with a peak incidence around age 65 years 
  • Presents similarly with vulvar irritation with pruritus, burning, and dyspareunia
  • Lesions are often multifocal involving other areas of perineum; appearance is eczematoid with well-demarcated and slightly raised edges
  • Differentiate by clinical presentation and confirm diagnosis with biopsy. Paget cells are pathognomonic
• Desquamative inflammatory vaginitis 
  • Chronic severe purulent vaginitis with nonspecific features and unknown cause
  • Occurs most commonly in perimenopausal women
  • May coexist with genitourinary syndrome of menopause
  • Presents similarly with vaginal discharge, dyspareunia, vaginal pain and burning, elevated vaginal pH, increased number of parabasal cells, and loss of Lactobacillus species dominance
  • Appearance includes diffuse erythema and inflammation of vulva and vagina
  • Unlike in genitourinary syndrome of menopause, 30% to 70% of patients have a spotted petechial or ecchymotic vaginal rash, and annular erythematous papules with a pale center may be noted 
  • Response to usual treatment of desquamative inflammatory vaginitis with topical clindamycin or topical steroids may help to further differentiate diagnoses; topical estrogen is ineffective treatment
• Trauma
  • Trauma to the vagina or vulva may present similarly with pain, dyspareunia, and even pruritus
  • Differentiate by history and physical examination
• Foreign body
  • Vaginal foreign body may present similarly with pain, pruritus, discharge, and dyspareunia
  • Differentiate by history and physical examination findings with presence of foreign body
• Vulvodynia 
  • Chronic pain in the vulva for more than 3 months 
  • Most women with condition experience localized vulvar pain provoked by vaginal penetration (eg, tampon use, intercourse)
    • Other comorbidities (eg, chronic pain syndrome, interstitial cystitis, fibromyalgia) may be present
    • This condition can occur at times other than at the menopausal transition
  • A neuropathic quality is characteristic of pain and itching is rare; physical examination is normal; pain may be elicited by light touch of vestibule with a cotton swab
  • Diagnosis is clinical, based on characteristic history, a positive cotton swab test eliciting pain in the vestibule, and exclusion of other diagnoses
• Vaginismus
  • Involuntary vaginal muscle spasm creates pain on vaginal penetration (eg, tampons, intercourse)
  • Cause may include undiagnosed vulvovaginal disorders or other factors (eg, prior sexual trauma, anxiety, cultural or religious beliefs)
  • May be a complication of or coexist with genitourinary syndrome of menopause
  • Presents similarly with vaginal pain and dyspareunia
  • Differentiating features include absence of pruritus and discharge; physical examination does not demonstrate cutaneous or mucosal abnormalities
  • Diagnose by clinical presentation; can confirm diagnosis by lack of spasm during examination under anesthesia 
• Urinary tract infection
  • Presents similarly with frequency, urgency, dysuria, and hematuria
  • Difficult to distinguish clinically without urinalysis
  • Findings consistent with urinary tract infection include presence of leukocytes and positive leukocyte esterase and/or nitrates
  • Confirm with urine culture

Treatment Goals

• Reduce urinary, genital, and sexual symptoms
• Improve functional limitations affecting sexual health and/or quality of life
• Prevent chronic urinary tract infections and other potential complications (eg, vaginal stenosis)

Disposition

Recommendations for specialist referral

• Refer to gynecologist for further diagnostic and treatment recommendations
  • Patients with recalcitrant disease not responding to first line measures
  • Patients with significant disease complications (eg, vaginal introital stenosis, pelvic organ prolapse)

Treatment Options

Mild to moderate symptoms

• First line treatment for most patients includes OTC lubricants and moisturizers
  • Nonprescription lubricants and moisturizers alone may be provide sufficient mild to moderate symptom relief 
  • Lubricants are recommended for short-term relief of vaginal dryness and discomfort associated with sexual activity 
    • Designed to reduce friction-related irritation to atrophic tissues during intercourse 
    • Products may be water-, silicone-, and oil-based
      • Oil-based products may degrade latex condoms
      • Water-based, hyperosmolar products may result in mucosal irritation
  • Recommend regularly using vaginal moisturizers in women with ongoing discomfort due to vaginal dryness 
    • Moisturizers mimic vaginal secretions (eg, increase vaginal mucosal moisture, reduce pH)
    • Used independently of sexual activity 
    • Recommended frequency of use is daily or every other day, depending on symptom severity 
    • Long-acting products may decrease vaginal pH to premenopausal levels 
  • Many options are available; products most closely resembling healthy vaginal pH, osmolality, and composition of secretions are preferred 
    • Ideal osmolality for water-based products is below 380 mOsm/kg; avoid hyperosmolar preparations. Very high osmolality (greater than 1200 mOsm/kg) may result in irritation, contact dermatitis, and cytotoxicity 
    • Choose products with pH within reference range for healthy adult women (3.8-4.5 pH); pH levels of 3.0 or less are poorly tolerated 
    • Hyaluronic acid products are described as an effective alternative to estrogen-based treatments, eg in women with contraindications to estrogen-based therapy; however, there is no evidence that these produce greater benefits than nonhyaluronic acid lubricants or moisturizers 
    • Avoid products with parabens, glycerin, warming properties, flavors, and spermicides owing to potential for tissue irritation 

Moderate to severe and persistent mild to moderate symptoms

• First line treatment is low-dose vaginal estrogen when patient has no contraindications 
  • Useful to treat symptoms unresponsive to nonprescription therapy (eg, nonprescription lubricants, moisturizers); may be used in addition to nonprescription treatments 
    • Vaginal estrogen is contraindicated in patients with undiagnosed vaginal bleeding, and its use is considered controversial in those with a history of a hormone-sensitive malignancy 
      • Involve oncologists in decisions regarding use of vaginal estrogen for women with estrogen-sensitive cancers 
    • Vaginal estrogen carries the same black box warnings as systemic estrogen with progestin, despite minimal systemic absorption and reassuring long-term observational studies 
      • Listed contraindications include:
        • Undiagnosed vaginal bleeding
        • Known or suspected breast cancer
        • Estrogen-dependent cancer
        • Endometrial hyperplasia or cancer
        • History of thromboembolism or known thrombophilia
        • Hypertension
        • Hyperlipidemia
        • Liver disease
        • History of stroke or venothrombotic events
        • Coronary artery disease
        • Pregnancy
        • Smoking in patients aged 35 years and older
        • Migraines with neurologic symptoms
        • Cholecystitis/cholangitis
    • Patients with contraindication to low-dose vaginal estrogen may require management with multiple nonhormonal modalities
  • Replenishes local estrogen receptors and reverses physiologic vaginal mucosal changes, improves vaginal secretions, lowers vaginal pH to restore healthy vaginal flora, prevents frequent urinary tract infections, and alleviates overall vulvovaginal symptoms 
  • More effective than systemic estrogen to treat vulvovaginal, urinary, and intercourse symptoms associated with genitourinary syndrome of menopause 
    • Many women who require estrogen replacement therapy for other menopausal symptoms also require supplemental topical estrogen for persistent symptoms of genitourinary syndrome of menopause 
    • Use of vaginal estrogen diminishes urinary urgency, urinary incontinence, and reduces risk of urinary tract infections 
  • Use lowest dose and frequency of vaginal estrogen therapy to effectively manage symptoms
    • Vaginal estrogen may be used intermittently for 1 to 3 months or may be used long-term 
    • Improvement may be noted within a few weeks of starting treatment; 8 to 12 weeks is required for most patients to experience maximum benefit of therapy 
    • Up to 90% of women report symptom improvement with low-dose vaginal estrogen therapy 
  • Various low-dose vaginal estrogen formulations (eg, cream, tablets, capsule, sustained-release estradiol-17β vaginal ring) with comparable efficacy and safety profiles are available 
    • Determine choice of formulation based on patient and physician preference 
    • Vaginally inserted tablets or capsules instead of cream may be preferred in situations requiring controlled dosing 
  • Systemic estrogen absorption is thought to be minimal; serum estradiol remains in the healthy menopausal range for creams, tablets, capsules, and estradiol-17β vaginal ring 
    • Despite minimal systemic absorption, the same warnings exist for vaginal estrogen preparations as systemic estrogen preparations for cardiovascular disease, thrombosis, endometrial cancer, breast cancer, and other hormone-sensitive cancers 
    • Minimal absorption may be a concern for women receiving aromatase inhibitors because even minimal absorption may affect efficacy of aromatase inhibitor therapy 
    • Estradiol acetate vaginal ring is an exception resulting in systemic hormone levels effective at treating vasomotor symptoms in addition to genitourinary syndrome of menopause symptoms 
  • Vaginal estrogen therapy is unlikely to pose risks for survivors of hormone-dependent cancers (eg, breast cancer, endometrial cancer) owing to minimal systemic absorption. Findings from clinical trials and observational studies are reassuring though not definitive; consider the following recommendations: 
    • Strongly preferred first line treatments are nonhormonal 
    • Individualized management must take into account both patient needs and oncologist recommendations 
    • Ultra-low-dose vaginal estrogen (preferably estriol) therapy may be used in select women with refractory symptoms that significantly affect quality of life for short duration after thorough consideration of risk-benefit ratio 
  • Data do not suggest increased risk for endometrial hyperplasia or cancer with unopposed low-dose vaginal estrogen 
    • Progestins are not indicated in most situations for endometrial protection in those using low-dose vaginal estrogen 
    • Consider yearly transvaginal ultrasonography for endometrial surveillance or prescribe yearly progesterone withdrawal for women at high risk for endometrial cancer (eg, obesity, use of higher doses than recommended) 
• Alternate management strategies
  • Ospemifene
    • Only selective estrogen receptor modulator approved to treat genitourinary syndrome of menopause 
      • Other available selective estrogen receptor modulators (eg, tamoxifen, raloxifene, bazedoxifene) are not approved to treat this syndrome; tamoxifen may cause vaginal dryness and dyspareunia
    • Synthetic nonsteroidal agent that exerts mixed estrogen agonist and antagonist effects on vulvovaginal tissue at doses of 60 mg daily; does not appear to target or affect breast or endometrial tissue 
    • Improves vaginal pH, vaginal dryness, vaginal maturation index, and dyspareunia; findings consistent with improved mucosal estrogen effects are noted on examination. Additionally, reduces bone turnover markers 
    • Approved to treat moderate to severe dyspareunia associated with genitourinary syndrome of menopause; option for some patients who cannot (eg, severe arthritis, obesity) or prefer not to use intravaginal treatment 
    • Although package insert stresses monitoring women taking ospemifene to treat endometrial cancer, risk of endometrial hyperplasia appears to be very low (0%-1%). Most data suggest ospemifene has favorable endometrial safety profile; addition of progestin not recommended 
    • Current recommendations suggest avoiding use in patients both with and at high risk for breast cancer; data are limited but suggest drug may exert antiestrogenic effect in breast tissue 
    • As with estrogen therapy, ospemifene increases risk of thromboembolism; avoid in patients at high risk of venous thromboembolism 
  • Vaginal dehydroepiandrosterone
    • Steroid prohormone that converts locally to testosterone and estrogen when applied to mucosal tissue
    • Improves vaginal pH and vaginal maturation index, and diminishes vaginal dryness and dyspareunia 
    • FDA-approved for dyspareunia associated with genitourinary syndrome of menopause 
    • Not associated with proliferative endometrial effects, and minimal increases in systemic hormone levels are noted 
    • However, vaginal dehydroepiandrosterone is not uniformly recommended for cancer survivors because studies assessing its safety in this population are limited 
  • Systemic estrogen therapy with or without progesterone
    • Appropriate when needed for other symptoms of menopause (eg, vasomotor symptoms, sleep and mood dysregulation) and protection from osteoporosis 
    • Progestogen is recommended for women without history of hysterectomy (presence of intact uterus)
    • Systemic hormone therapy relieves vaginal symptoms for most patients; however, 10% to 15% may require addition of low-dose vaginal estrogen 
    • Systemic therapy is not expected to improve urinary incontinence and may increase risk for stress urinary incontinence 
    • Contraindicated in patients with estrogen-sensitive cancers and in those with high risk of thromboembolic disease 
  • Bazedoxifene and conjugated estrogen combination
    • Bazedoxifene plus conjugated estrogens is designated as a tissue-selective estrogen complex
      • Bazedoxifene (a selective estrogen receptor modulator) alone does not improve vaginal symptoms of genitourinary syndrome of menopause
      • No progestin is needed to allow for endometrial shedding in women with intact uterus given selectivity profile of bazedoxifene (bazedoxifene has limited, if any, stimulation of uterine endometrium)
    • Significant data support improvement in symptoms; rate of endometrial hyperplasia is similar to placebo 
  • Tibolone
    • Synthetic steroid that has mild estrogenic, progestogenic, and androgenic properties
    • Improves vaginal maturation index, increases sexual desire, and decreases nocturia and urinary urgency 
    • Data are limited regarding cardiovascular effects; initial data indicate effects similar to estrogen plus progesterone
    • Available in many countries to treat menopausal symptoms, but not available in the United States 
  • Topical lidocaine 
    • Apply to introitus a few minutes before sexual activity to diminish pain with intercourse
    • May be used as an adjunct to lubricants and physical therapy in breast cancer survivors with dyspareunia
  • Energy-based therapies
    • Lasers therapy and radio-frequency devices are being studied as treatment but none have FDA approval specifically to treat genitourinary syndrome of menopause
    • Based on preliminary limited data, laser therapy is promising; however, these are not recommended until longer, larger studies confirm safety and efficacy 
      • In a 2018 Safety Communication, FDA issued a warning about the use of these devices for vaginal cosmetic purposes, stating that the effectiveness and safety of the devices have not yet been established 
    • Used to stimulate remodeling of vaginal connective tissue and improve vaginal epithelium (eg, promote increased thickening, improve glycogen storage) 
    • Fractional CO2 and Erbium:YAG lasers have demonstrated improvements in vaginal dryness, discomfort, pruritus, and dyspareunia
  • Testosterone 
    • Topical testosterone cream has been used for the treatment of vulvovaginal conditions such as lichen sclerosus and vestibulodynia
    • Systemic testosterone may be indicated for the treatment of hypoactive sexual desire disorder/dysfunction use in postmenopausal women 
    • A small 4-week pilot study found that vaginal testosterone improved dyspareunia, vaginal dryness in postmenopausal women with breast cancer
    • Systemic or local testosterone are not recommended for treatment of genitourinary syndrome of menopause until further studies establish safety and efficacy 
  • Vaginal oxytocin gel
    • Small studies have yielded conflicting results regarding effect on menopausal symptoms; one study showed no more effective than an equivalent non–hormone-containing gel 

Drug therapy

• Vaginal estrogen
  • Estradiol cream
    • Guideline-recommended dosing
      • Estradiol Vaginal cream; Adult menopausal and postmenopausal females: Initially, 0.5 to 1 g (50-100 mcg of estradiol) vaginally once daily for 2 weeks; then maintenance dosing of 0.5 to 1 g (50-100 mcg of estradiol) vaginally 1 to 3 times per week.
    • FDA label dosing
      • Estradiol Vaginal cream; Adult menopausal and postmenopausal females: Initially, 2 grams to 4 grams (200 mcg to 400 mcg of estradiol) vaginally once daily for 1 to 2 weeks; then gradually reduce over 1 to 2 weeks. Usual maintenance: 1 gram (estradiol 100 mcg) vaginally 1 to 3 times per week. Treatment is cyclic (3 weeks on, then 1 week off).
  • Estradiol vaginal inserts
    • Vagifem, Yuvafem vaginal tablets only
      • Estradiol Vaginal insert; Adult menopausal and postmenopausal females: Insert 1 tablet (10 mcg) vaginally once daily for 2 weeks into the upper third of the vaginal vault using the supplied applicator. After 2 weeks, insert 1 tablet vaginally twice weekly (e.g., every Tuesday and Friday).
    • Imvexxy vaginal insert only
      • Estradiol Vaginal insert; Adult menopausal and postmenopausal females: Place 1 insert vaginally once daily at approximately the same time of day for 2 weeks, followed by 1 insert twice weekly (e.g., Monday and Thursday). Generally, initiate with the 4 mcg insert. Max: 10 mcg/dose vaginally. Use the lowest effective dose.
  • Estradiol ring
    • Estradiol Vaginal insert; Adult menopausal and postmenopausal females: Insert 1 vaginal ring (delivering estradiol 7.5 mcg/24 hours) deep into the upper third of the vaginal vault. Keep in place continuously for 3 months, then remove. If appropriate, insert a new ring. The dosage of Estring vaginal ring is not effective at treating vasomotor symptoms.
  • Conjugated estrogen cream
    • Guideline-recommended dosing
      • Conjugated Estrogens Vaginal cream; Adult menopausal and postmenopausal females: Initially, 0.5 to 1 g vaginally once daily for 2 weeks; then maintenance dosing of 0.5 to 1 g vaginally 1 to 3 times per week. 
    • FDA label dosing
      • Conjugated Estrogens Vaginal cream; Adult menopausal and postmenopausal females: Initially, 0.5 grams vaginally once daily for 21 days; then, no treatment for 7 days. The dose may be increased up to 2 grams/day vaginally depending on response. Repeat cyclically. Use lowest effective dose and reevaluate need for treatment every 3 to 6 months. For moderate to severe dyspareunia, a dose of 0.5 grams vaginally twice weekly (e.g., every Monday and Thursday) may be sufficient in some patients; otherwise, consider the same dose as for other vaginal symptoms. When isolated genitourinary symptoms caused by menopause are present, treatment guidelines recommend low-dose vaginal estrogens over systemic estrogens as first-line therapy.
  • Estriol cream
    • Not FDA approved for usage in the United States; however, has been studied and used in Europe.
    • Not commercially available in the United States.
    • Estriol Vaginal cream; Adult menopausal and postmenopausal females: Initially 0.5 mg vaginally once daily for 2 weeks; then maintenance dosing of 0.5 mg vaginally 2 to 3 times weekly. Use lowest effective dose. 
• Ospemifene
  • Ospemifene Oral tablet; Adult menopausal and postmenopausal females: 60 mg PO once daily with food. Consider the addition of a progestin in postmenopausal women with an intact uterus to reduce risk for endometrial hyperplasia. Assess the need for continued treatment periodically.
• Vaginal dehydroepiandrosterone (prasterone) 0.25% to 1.0% 
  • Prasterone Vaginal insert; Adult menopausal and post-menopausal females: 1 insert (6.5 mg) administered vaginally once daily at bedtime, using the provided applicator.
• Systemic hormone therapy
  • Oral
    • Estradiol Oral tablet; Adult menopausal and postmenopausal females: 0.5 mg to 2 mg PO once daily. Usual initial dose: 1 or 2 mg PO once daily. Less than 1 mg/day PO may suffice for vaginal/vulvar symptoms only. Administration should be cyclic (e.g., 3 weeks on and 1 week off). In women with an intact uterus, estrogen may be given cyclically or combined with a progestin for at least 10 to 14 days per month.
    • Conjugated Estrogens Oral tablet; Adult menopausal and postmenopausal females: Initially, 0.3 mg PO once daily. May titrate if needed. Use lowest effective dose. Few patients need up to 1.25 mg/day PO. Doses of less than 0.45 mg/day may be adequate for vaginal/vulvar symptoms only. Continuous, unopposed estrogen administration is acceptable in women without a uterus. In women with an intact uterus, estrogen may be given cyclically (e.g., 25 days of month then 5 days off) or combined with a progestin for at least 10 to 14 days per month to minimize the risk of endometrial hyperplasia. However, taking estrogens with progestins may have additional health risks for the patient; risk must be determined individually. Reevaluate every 3 to 6 months to determine if the dose and continued hormone replacement is appropriate.
    • Conjugated Estrogens, Medroxyprogesterone Acetate Oral tablet; Adult menopausal and postmenopausal females: 1 tablet PO once daily. Dosage titration options include: A) 0.3 mg conjugated estrogen/1.5 mg medroxyprogesterone acetate tablet, B) 0.45 mg conjugated estrogen/1.5 mg medroxyprogesterone acetate tablet, C) 0.625 mg conjugated estrogen/2.5 mg medroxyprogesterone acetate tablet, or D) 0.625 mg conjugated estrogen/5 mg medroxyprogesterone acetate tablet. Titrate as needed, using the lowest effective dose. Cycles are repeated continuously, using a new blister card every 28 days. Reevaluate at 3 to 6 month intervals to determine appropriate dose and need for continued treatment.
  • Transdermal patch
    • Estradiol Transdermal patch – weekly; Adult menopausal and postmenopausal females: 1 patch (delivering 0.025 mg, 0.0375 mg, 0.05 mg, 0.06 mg, 0.075 mg, or 0.1 mg per day) applied and replaced every 7 days. Usual initial dose is 0.0375 mg/day or 0.05 mg/day. Use lowest effective dose.
    • Estradiol Transdermal patch – biweekly; Adult menopausal and postmenopausal females: 1 patch (delivering 0.025 mg, 0.0375 mg, 0.05 mg, 0.075 mg, or 0.1 mg per day); replace twice weekly (every 3 to 4 days). Usual initial dose is 0.0375 mg/day or 0.05 mg/day; see individual patch recommendations.
• Bazedoxifene and conjugated estrogen combination
  • Conjugated Estrogens, Bazedoxifene Oral tablet; Adult menopausal and postmenopausal females: 1 tablet PO once daily (conjugated estrogens 0.45 mg and bazedoxifene 20 mg per tablet). Reevaluate every 3 to 6 months to determine if the dose and continued hormone replacement are appropriate.
• Tibolone
  • In June 2006, tibolone did not receive FDA approval in the United States for treatment of symptoms related to menopause. Tibolone is available in Europe and many other countries globally under the trade name Livial and is approved in European countries for relief of vasomotor symptoms related to menopause and for the prevention of osteoporosis in postmenopausal women.
  • Tibolone Oral tablet; Adult menopausal and postmenopausal females: 2.5 mg PO once daily.
• Lidocaine 
  • Lidocaine Hydrochloride 5% Topical gel or ointment; Adults: Apply to the vestibule with a cotton ball 30 minutes before intercourse as needed for adequate control of symptoms.
• Topical estradiol therapies for genitourinary syndrome of menopause.TreatmentBrand nameInitial dosageMaintenance dosageCommentsVaginal creamEstradiol-17βEstrace0.5-1 g daily for 2 weeks0.5-1 g, 1-3 times weeklyInitial dose approved by FDA is higher (2-4 g daily)Conjugated estrogensPremarin0.5-1 g daily for 2 weeks0.5-1 g, 1-3 times weeklyFDA approval calls for cyclical administration and higher dose (for genitourinary syndrome of menopause: 0.5-2 g daily for 21 days then off for 7 days; for dyspareunia: 0.5 g daily for 21 days then off for 7 days or 0.5 g twice weekly)Vaginal insertEstradiol hemihydrateVagifem, Yuvafem10 mcg tablet insert daily for 2 weeks1 twice weeklyEstradiol tear-shaped vaginal insertsImvexxy4 mcg insert daily for 2 weeks4-10 mcg insert twice weeklyFDA approved May 2018
  
  Initial dose is 4 mcg, may titrate dose based on clinical response; Max dose: 10 mcg/dose vaginallyDehydroepiandrosterone Intrarosa6.5 mg once daily6.5 mg once dailySteroid prohormone with effects from local conversion to testosterone and estrogen; associated with minimal increase in systemic hormone levels and may be safer option than vaginal estrogen in patients with contraindications to use of estrogen (eg, hormone-sensitive breast and endometrial cancer survivors)Vaginal ringEstradiol-17βEstringInsert for 90 daysChange every 90 days2 mg releases approximately 7.5 mcg dailyEstradiol acetateFemringInsert for 90 daysChange every 90 daysVaginal delivery provides systemic hormone levels to treat vasomotor symptoms and genitourinary syndrome of menopause; 12.4 mg releases 0.05 mg and 24.8 mg releases 0.1 mg dailyCaption: Systemic estrogen absorption is minimal with low-dose vaginal estrogen treatments. Serum estradiol remains in menopausal reference range for creams, tablets, capsules, and estradiol-17β vaginal ring; estradiol acetate vaginal ring is an exception and does result in systemic hormone levels effective at treating vasomotor symptoms.
• Citation: Data from Faubion SS et al: Genitourinary syndrome of menopause: management strategies for the clinician. Mayo Clin Proc. 92(12):1842-9, 2017; and TherapeuticsMD: Imvexxy – estradiol insert [prescribing information]. National Library of Medicine DailyMed website. Updated December 6, 2019. Accessed February 4, 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=104be9f2-a8f6-430e-9e01-2ee7cc1861f1.

Nondrug and supportive care

Other supportive measures

• Educate patient about cause of symptoms and options for treatment
  • Advise that symptoms are not likely to improve without treatment, and untreated pain may lead to worsening sexual dysfunction 
• Suggest importance of healthy sexual choices in effort to maintain vaginal health 
  • Regular penetrative sexual activity with or without a partner can help maintain vaginal health; patients can use vibrators therapeutically to stimulate blood flow and maintain vaginal function 
  • The lubricative response to sexual arousal is believed to aid maintenance of vaginal elasticity 
• Risk factor modification (eg, smoking cessation, wearing loose undergarments and pants) may help diminish symptoms 
• Specific symptomatic care measures include:
  • May use lubricated dilators for vaginal stretching to treat patients with vaginal constriction and vaginismus 
  • May use pelvic floor physical therapy to treat patients with pelvic floor muscle dysfunction, urinary incontinence, vaginal constriction, or vaginismus 
  • Consider sex therapy for patients with refractory sexual dysfunction or dyspareunia

Procedures

• Laser therapies
  • Not yet FDA approved to treat genitourinary syndrome of menopause. Although large-scale and rigorous safety and efficacy data are lacking, laser therapy is being used off-label in clinical settings 
  • Considered a possible alternate approach for patients with absolute contraindications to available hormonal treatments or inability or unwillingness to use moisturizers, lubricants, or vaginal estrogen
  • Data are not available regarding prevention of recurrent urinary tract infection associated with genitourinary syndrome of menopause
  • Optimal number of treatments is unclear; typical course of treatment includes 3 treatments, each 1 month apart 
  • Available laser types include:
    • Fractional microablative carbon dioxide laser
      • Limited data support short-term efficacy 
      • May improve symptoms of vaginal dryness, pruritus, dysuria, and dyspareunia 
      • Serious adverse effects have not been reported 
      • Study of 50 women reported sustained effects at 12 weeks with no adverse effects 
      • Improvement in genitourinary syndrome of menopause symptoms and urinary and sexual function at 6-month follow-up similar to that seen with vaginal estrogen 
    • Erbium:YAG laser
      • Limited data support short-term efficacy up to 18 to 24 months 
      • May improve symptoms of vaginal dryness, dyspareunia, and stress urinary incontinence 
      • Serious adverse effects have not been reported 

Special populations

• Patients with breast cancer or at high risk for breast cancer 
  • Treatment is individualized:
    • First line treatments are nonhormonal (eg, lubricants, and moisturizers, dilators, pelvic floor therapy, topical lidocaine)
    • If symptoms are severe or recalcitrant, laser therapy may be offered
  • Considerations include cancer recurrence risk, symptom severity, response to previous therapy, and personal preference
  • Vaginal hormone therapies may be an option for some women for whom nonpharmacologic and nonhormone treatments do not work after discussing risks and benefits with patient and reviewing strategy with treating oncologist
    • Use the less potent form of estrogen, estriol, in lowest available doses 
  • Varying consensus recommendations exist for women with estrogen-receptor positive breast cancers, women with triple-negative breast cancers, women with metastatic disease, and women at high risk for breast cancer
  • Use extreme caution in women taking aromatase inhibitors for breast cancer 
    • Aromatase inhibitors, used in the treatment of postmenopausal breast cancer, are used to decrease serum estradiol levels 
    • Patients being treated with aromatase inhibitors who are also using the estradiol ring or 25-mcg vaginal tablets (currently off-market in the United States) have small but significant increases in serum estradiol levels 
• Women after treatment of endometrial cancer
  • There is a theoretical risk of promoting recurrence of endometrial cancer with use of hormone therapy in survivors of endometrial cancer, as this carcinoma is usually estrogen receptor–positive
  • Local and systemic menopausal hormone therapy is not recommended for women with advanced endometrial cancer 
  • There is a lack of high-level evidence demonstrating safety of either systemic or local menopausal hormone therapy in women with history of early-stage endometrial cancer; thus, most experts consider there to be insufficient evidence to inform decisions about hormone therapy for this population 
    • Retrospective series show incidence of recurrence of endometrial cancer in women who are prescribed vaginal estrogen is approximately 7% 

Monitoring

• Clinically monitor for efficacy of treatment and potential adverse treatment effects
  • Assess annually for treatment efficacy, additional clinical needs, and any necessary additional treatment options 
  • Laboratory testing (eg, vaginal maturation index, vaginal pH) is not routine unless manifestations are recalcitrant to typical measures or a concomitant diagnosis is suspected
  • Assess for adherence issues in patients with minimal or no response to typical measures 
    • Some women discontinue low-dose vaginal estrogen cream within several months of starting for various reasons, including messiness, inconvenience, cost, and safety concerns
    • Continued education and change of formulation may effectively address barriers to continued treatment
  • Monitor for vaginal bleeding during treatment with vaginal estrogen 
    • Evaluate any reported spotting or bleeding with pelvic imaging (eg, ultrasonography) and endometrial biopsy when indicated
• Consider yearly transvaginal ultrasonography to assess for endometrial proliferation in the following patients: 
  • Those at high risk for endometrial cancer who use vaginal estrogen therapy
  • Those who use a higher-than-recommended dose of vaginal estrogen therapy

Complications

• Vaginal trauma (eg, laceration, hemorrhage)
• Vaginal stenosis and shortening
• Introital stenosis
• Vaginismus (involuntary contraction of muscles surrounding vagina)
• Increased risk for developing both vaginal and urinary tract (including chronic) infections
• Prolapse of urethra, uterus, pelvic organ, or vaginal vault
• Urethral meatal stenosis, urethral atrophy, and retraction of urethral meatus inside vagina (associated with vaginal voiding)
• Urethral polyp or caruncle
• Cystocele and rectocele
• Chronic pelvic pain
• Sexual dysfunction
  • May develop secondary to dyspareunia and vaginismus
  • May manifest as loss of interest in sex and cessation of sexual activity
  • Reported up to 4 times more frequently in women with symptoms of syndrome than in women without symptoms of syndrome 

Prognosis

• Syndrome is chronic and progressive; manifestations are unlikely to improve or resolve without treatment and often worsen with increasing duration of hypoestrogenism 
• Prognosis is excellent in women who have mild symptoms controllable by lubricants and/or moisturizers
• Prognosis and symptom control is excellent in the vast majority of women with use of topical estrogen therapy
  • Up to 90% of women report symptom improvement with low-dose vaginal estrogen therapy 
  • Expect most genital, urinary, and sexual symptoms to improve with low-dose vaginal estrogen; however, low-dose vaginal estrogen alone does not effectively treat urinary incontinence 

Screening

At-risk populations

• Perimenopausal, menopausal, and postmenopausal women
• Patients with medication-induced hypoestrogenemia, eating disorders, hypogonadism, primary ovarian insufficiency, premature ovarian failure, or hyperprolactinemia
• Patients who are lactating

Screening tests

• Ask all women who are at-risk if they have symptoms of genitourinary syndrome of menopause; encourage regular gynecologic visits
  • Ask about sexual concerns or painful intercourse; recognize that both urinary and genital symptoms may develop from genitourinary syndrome of menopause
  • US Preventive Services Task Force recommendations include:
    • Gynecologic examination with Papanicolaou test every 5 years if HPV cotesting is done or every 3 years if HPV cotesting is not done, for women aged 21 to 65 years 
    • Sufficient evidence is not available to recommend screening pelvic examinations in any age group 
  • American College of Obstetrics and Gynecology recommendations include:
    • No recommendations for or against pelvic examinations in asymptomatic patients 
    • Shared decision-making between asymptomatic women and their physicians 
    • Pelvic examinations, when indicated by medical history or symptoms 
    • Screening women who have current or history of gynecologic malignancy, cervical dysplasia, or diethylstilbestrol exposure, according to guidelines specific to those conditions 
    • At least yearly visits with gynecologist for well-woman care, even if a pelvic examination is not required. Provides an opportunity to inquire about symptoms of genitourinary syndrome of menopause 
      • Pelvic examinations allow for diagnosis of vulvar lesions and dermatologic conditions, vulvar neoplasia, anogenital cancers, and vaginal atrophy that could be missed if not performed

Prevention

• Genitourinary syndrome of menopause may be prevented by systemic hormone therapy in women who require it for other symptoms or conditions 

References

1: Gandhi J et al: Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol. 215(6):704-11, 2016 Reference